Complete NMR Elucidation of Two N-Protected Trishomocubane Hydantoins and the Ethyl Ester of the Corresponding Amino Acid

Abstract

In an attempt to resolve a racemic mixture of a trishomocubane hydantoin, the synthesis of a pair of novel diastereomers was obtained by protecting the racemic hydantoin with chlorocarbonic acid-(−)(R)-sec-butyl ester. An achiral i-propyl ester was first used to establish the procedure. The NMR elucidation of both the chiral and achiral N-protected hydantoins is described. Some proton and carbon NMR shifts on the cage are reversed when relative small changes on the protection group are introduced. The chiral centre on the protective group induced splitting of some carbon signals in the 13C spectrum on the cage skeleton, but effective separation of the diastereomers could not be obtained. In a further attempt to demonstrate the potential use of the trishomocubane amino acid in peptide synthesis, the ethyl ester of the cage amino acid was synthesised. The structures of the amino acid derivatives were elucidated with 2D NMR techniques and the assignment of the NMR data is presented.